Diisopropylethylamine → HCID 178461916, compound

HRID 243308Notes

Reaction equation

HRID 243308 reaction equation
[Cl:1][C:2]1[C:7]2[N:8]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:9]([C@@H:11]([NH2:13])[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.Cl[C:21]1[N:29]=[CH:28][N:27]=[C:26]2[C:22]=1[N:23]=[CH:24][N:25]2C1CCCCO1.CCN(C(C)C)C(C)C>>[Cl:1][C:2]1[C:7]2[N:8]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:9]([C@@H:11]([NH:13][C:21]3[N:29]=[CH:28][N:27]=[C:26]4[C:22]=3[N:23]=[CH:24][NH:25]4)[CH3:12])=[N:10][C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

4

Reactant 3

HCID 81531DiisopropylethylamineHCID 977406-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 68157936(S)-1-(7-Chloro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine

Product 1

HCID 178461916HCID 178461916, compound

Conditions

Temperature
90 °C

Procedure

A mixture of (S)-1-(7-chloro-1-phenyl-1H-benzoimidazol-2-yl)ethylamine from Example 19 (482 mg, 1.77 mmol), 6-chloro-9-(tetrahydropyran-2-yl)-9H-purine (466 mg, 1.95 mmol) and DIPEA (0.91 mL, 5.32 mmol) in IMS (3.5 mL) was stirred in a sealed vial for 48 h at 90° C. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was loaded into an Isolute® SCX-2 which was washed with MeOH followed by 2M NH3/MeOH. The product containing fractions (basic and methanolic) were combined and concentrated in vacuo. Purification by Isolute® SCX-2 was repeated a second time and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM). The basic fractions were combined and concentrated in vacuo and the residue was refluxed in MeOH. After cooling to RT the solid was filtered off and washed with EtOAc affording 138 as a white solid (379 mg, 55%). LCMS: RT 3.65 min [M+H]+ 390.0. 1H NMR (DMSO, 400 MHz): δ 8.20-8.06 (2H, m), 7.94 (1H, s), 7.69-7.36 (6H, m), 7.24-7.19 (2H, m), 5.26 (1H, bs), 1.10 (3H, d, J=7.00 Hz)

Workup

  1. temperatureAfter cooling to RT
  2. customvolatiles were removed under reduced pressure
  3. washwas washed with MeOH
  4. additionThe product containing fractions (basic and methanolic)
  5. concentrationconcentrated in vacuo
  6. customPurification by Isolute® SCX-2
  7. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-10% 2M NH3/MeOH in DCM)
  8. concentrationconcentrated in vacuo
  9. temperaturethe residue was refluxed in MeOH
  10. temperatureAfter cooling to RT the solid
  11. filtrationwas filtered off
  12. washwashed with EtOAc affording 138 as a white solid (379 mg, 55%)

Sources & evidence

ORD record
ord-e86b588a56824e3ca1d01be1eca336f0
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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